Zollinger–Ellison syndrome

Zollinger–Ellison syndrome
Classification and external resources
Endoscopy image of multiple small ulcers in the distal duodenum in a patient with Zollinger–Ellison syndrome
ICD-10	E16.4
ICD-9	251.5
MedlinePlus	000325
eMedicine	med/2437 ped/2472
MeSH	D015043

Zollinger–Ellison Syndrome (ZES) is caused by a non–beta islet cell, gastrin-secreting tumor of the pancreas that stimulates the acid-secreting cells of the stomach to maximal activity, with consequent gastrointestinal mucosal ulceration. ZES may occur sporadically or as part of an autosomal dominant familial syndrome called multiple endocrine neoplasia type 1 (MEN 1). The primary tumor is usually located in the pancreas, duodenum or abdominal lymph nodes, but ectopic locations have also been described (e.g., heart, ovary, gallbladder, liver, kidney).

Pathophysiology

Gastrin works on stomach parietal cells causing them to secrete more hydrogen ions into the stomach lumen. In addition, gastrin acts as a trophic factor for parietal cells, causing parietal cell hyperplasia. Thus there is an increase in the number of acid-secreting cells, and each of these cells produces acid at a higher rate. The increase in acidity contributes to the development of multiple peptic ulcers in the stomach and duodenum (first portion of the small bowel).

Presentation

Patients with Zollinger–Ellison syndrome may experience abdominal pain and diarrhea. The diagnosis is also suspected in patients without symptoms who have severe ulceration of the stomach and small bowel, especially if they fail to respond to treatment.

Gastrinomas may occur as single tumors or as multiple, small tumors. About one-half to two-thirds of single gastrinomas are malignant tumors that most commonly spread to the liver and lymph nodes near the pancreas and small bowel. Nearly 25 percent of patients with gastrinomas have multiple tumors as part of a condition called multiple endocrine neoplasia type I (MEN I). MEN I patients have tumors in their pituitary gland and parathyroid glands, in addition to tumors of the pancreas.

Symptoms

• Chronic diarrhea, including steatorrhea (fatty stools)
• Pain in the esophagus, especially between and after meals at night
• Nausea
• Wheezing
• Vomiting blood (digested blood)
• Malnourishment
• Loss of weight due to loss of appettite

Diagnosis

Clinical suspicion of Zollinger–Ellison syndrome may be aroused when the above symptoms prove resistant to treatment, when the symptoms are especially suggestive of the syndrome, or endoscopy is suggestive. The diagnosis of Zollinger–Ellison syndrome is made by several laboratory tests and imaging studies.

• Secretin stimulation test, which measures evoked gastrin levels
• Fasting gastrin levels, on at least three separate occasions
• Gastric acid secretion and pH. Normal basal gastric acid secretion is less than 10 mEq/hour, while in Zollinger–Ellison syndrome it is usually more than 15 mEq/hour.
• An increased level of chromogranin A is a common marker of neuroendocrine tumors

In addition, the source of the increased gastrin production must be discovered. This is either done using MRI or somatostatin receptor scintigraphy, the investigation of choice.

Therapy

Proton pump inhibitors (such as omeprazole and lansoprazole) and histamine H2-receptor antagonists (such as famotidine and ranitidine) are used to slow down acid secretion. PPI and H2 antagonist are relatively ineffective for pharmacologic treatment. Octreotide is the best drug for pharmacologic management. Cure is only possible if the tumors are surgically removed, or treated with chemotherapy.

History

The syndrome was first described by the Norwegian doctor Roar Strøm in 1952. Therefore the syndrome sometimes also is called Strøm-Zollinger–Ellison syndrome in the literature. The syndrome was later on described in 1955 by Robert Zollinger and Edwin Ellison, surgeons at The Ohio State University.